This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. CD4-specific DARPin 57.2, a potent inhibitor of HIV and SIV infection in vitro, was injected into 9 rhesus macaques infected with SHIV-RT. DARPin-bound CD4-positive cells were detected in the peripheral blood as early as 30 minutes after the injection and until the 24 hour mark. DARPin 57.2 bound the various CD4-expressing cell types both in vivo and in vitro with the amount of binding directly proportional to the amount of CD4 on the cell surface. DARPin 57.2 was cleared from the plasma within 24 hours after injection. We demonstrate that the CD4-specific DARPin can rapidly and selectively bind its target cells in vivo, warranting further studies on possible clinical use of the DARPin technology.